Author's Take

In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The JCI accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the
Author's Take Guidelines page.

Anti-PD-1 therapy with inhibitors such as pembrolizumab has proven beneficial for multiple types of cancers. Not all patients respond to PD-1 blockade; therefore, strategies to better predict individual response to anti-PD-1 would be of great clinical benefit. In this episode, Terri McClanahan and Jared Lunceford discuss their work, which has led to the identification of a gene expression profile that correlates with clinical response to pembrolizimab. Importantly, the presence of this T cell-inflamed gene expression profile in patients prior to treatment was shown to be indicative of response in multiple cohorts and cancer types.

The accumulation of macrophages with a proinflammatory phenotype in adipose tissue is a driver of obesity-associated metabolic disease. While adipose tissue macrophages are found in the lean state, these cells have an alternatively activated (M2) phenotype. In this episode, Tamás Röszer and colleagues demonstrate that adipose tissue macrophages express a receptor for the appetite-reducing neuropeptide FF and that and that neuropeptide FF promotes M2 activation and proliferation. Additionally, obesity was associated with reduced levels of circulating neuropeptide FF. Together, the results of this study reveal an important role for neuropeptide FF in maintaining metabolically beneficial macrophages in adipose tissue.

One of the leading factors in breast cancer-related death, is tumor recurrence despite apparently successful therapeutic intervention. Recurrent disease is linked to the presence of a minimal population of residual cancer cells that are hard to detect; therefore, little is known about these cells. In this episode, Martin Jechlinger and colleagues present several lines of evidence to show that residual cells have a distinct transcriptional profile that results in changes in metabolism and elevated ROS production. Together, these results provide a better understanding of these cells and suggest potential targeting strategies.

Invariant natural killer T (iNKT) cells are a prominent component of the liver-resident immune cell population. These cells are involved in both liver regeneration and regulation of the local immune response; however, little is known about how iNKT cells are maintained within the liver. In this episode, Xian Li reveals that stimulation of cell surface receptor OX40 induces a pyroptotic cell death in liver iNKT cells that exacerbates liver injury and inflammation. The results of this study support the OX40 pathway as a potential therapeutic target for limiting liver damage.

Mice with defects in the stem cell factor receptor Kit lack mast cells, which have been implicated in a variety of inflammatory diseases such as arthritis. There are strain-specific differences in how mast cell-deficient animals manifest model diseases, leading to questions about the role of mast cells in certain pathologies. In this episode, Peter Nigrovic and colleagues investigate differences in mast cell-deficient mice that lead to differential susceptibility to IgG-induced arthritis. Using a series of bone marrow and cell transplantation experiments, Nigrovic and coworkers reveal that marrow and stromal context determine the role of mast cells in inflammation and that megakaryocytes can directly mediate inflammation.